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Obesity is in epidemic proportions in many parts of the world, contributing to increasing rates of non-alcoholic fatty liver disease (NAFLD). NAFLD represents a range of conditions from the initial stage of fatty liver to non-alcoholic steatohepatitis (NASH), which can progress to severe fibrosis, through to hepatocellular carcinoma. There currently exists no treatment for the long-term management of NAFLD/NASH, however, dietary interventions have been investigated for the treatment of NASH, including several polyphenolic compounds. Ellagic acid is one such polyphenolic compound. Nutraceutical food abundant in ellagic acid undergoes initial hydrolysis to free ellagic acid within the stomach and small intestine. The proposed mechanism of action of ellagic acid extends beyond its initial therapeutic potential, as it is further broken down by the gut microbiome into urolithin. Both ellagic acid and urolithin have been found to alleviate oxidative stress, inflammation, and fibrosis, which are associated with NAFLD/NASH. While progress has been made in understanding the pharmacological and biological activity of ellagic acid and its involvement in NAFLD/NASH, it has yet to be fully elucidated. Thus, the aim of this review is to summarise the currently available literature elucidating the therapeutic potential of ellagic acid and its microbial-derived metabolite urolithin in NAFLD/NASH.

Scope: Higher intake of cruciferous and allium vegetables is associated with lower cardiometabolic risk. Little research has investigated the cardiometabolic effects of S-methyl cysteine sulfoxide (SMCSO), found abundant in these vegetables. This study hypothesizes that SMCSO will blunt development of metabolic syndrome features in mice fed high-fat feed. Methods and results: Fifty C57BL/6 male mice are randomly assigned to standard-chow, high-fat, or high-fat supplemented with low-SMCSO (43 mg kg−1 body weight [BW] day−1), medium-SMCSO (153 mg kg−1 BW day−1), or high-SMCSO (256 mg kg−1 BW day−1) for 12-weeks. High-fat with SMCSO did not prevent diet-induced obesity, glucose intolerance, or hypercholesterolemia. Mice fed high-fat with SMCSO has higher hepatic lipids than mice fed standard-chow or high-fat alone. Urinary SMCSO increases at 6- and 12-weeks in the low-SMCSO group, before reducing 46% and 28% in the medium- and high-SMCSO groups, respectively, at 12-weeks, suggesting possible tissue saturation. Interestingly, two SMCSO-fed groups consume significantly more feed, without significant weight gain. Due to limitations in measuring consumed feed, caution should be taken interpreting these results. Conclusion: SMCSO (43–256 mg kg−1 BW day−1) does not ameliorate metabolic syndrome features in high-fat fed mice. Substantial knowledge gaps remain. Further studies should administer SMCSO separately (i.e., gavage), with metabolic studies exploring tissue levels to better understand its physiological action.

BACKGROUND: Bleeding risk brought by intensive lipid-lowering therapy and low low-density lipoprotein cholesterol is concern-ing, while evidence regarding the relationship between remnant cholesterol and bleeding is frightening. This study aimed to investigate the association between remnant cholesterol at admission and an in-hospital bleeding event after acute ischemic stroke or transient ischemic attack (TIA). METHODS AND RESULTS: A total of 3222 eligible patients admitted to Shanghai Huashan Hospital between 2015 and 2021 with complete lipid data were analyzed. Patients were classified into low (<20.0 mg/dL), moderate (20.0–29.9 mg/dL), and high (≥30 mg/dL) groups by remnant cholesterol. The mean age of patients was 63.0± 13.1 years, including 2301 (71.4%) men and 651 (20.2%) with TIA. The median (interquartile range) of remnant cholesterol was 18.6 (13.5–25.9) mg/dL. After adjustment for confounding variables, patients with low remnant cholesterol had a higher risk of bleeding events (odds ratio, 2.56 [95% CI, 1.12–6.67]) than those with moderate remnant cholesterol. The high remnant cholesterol group was not significantly associated with bleeding risk. Combined assessment of low-density lipoprotein cholesterol and remnant cholesterol further identi-fied patients with the highest risk of bleeding events. CONCLUSIONS: Low remnant cholesterol levels were associated with bleeding events during the acute stage of ischemic stroke and TIA. The assessment of remnant cholesterol could inform the bleeding risk during hospitalization both for patients and physicians in clinical practice.

Background: Suboptimal Health Status (SHS) is the physical state between health and disease. This study aimed to fill in the knowledge gap by investigating the prevalence of SHS and psychological symptoms among unpaid carers and to identify SHS-risk factors from the perspective of predictive, preventive and personalised medicine (PPPM). Methods: A cross-sectional study was conducted among 368 participants who were enrolled from Australia, including 203 unpaid carers as cases and 165 individuals from the general population as controls. SHS scores were measured using SHSQ-25 (Suboptimal Health Status Questionnaire-25), whilst psychological symptoms were measured by DASS-21 (Depression, Anxiety and Stress Scale-21). Chi-square was used to measure SHS and psychological symptom prevalence. Spearman correlation analysis was utilised to identify the relationship between SHSQ-25 and DASS-21 scores. Logistic regression analysis was used for multivariate analysis. Results: The prevalence of SHS in carers was 43.0% (98/203), significantly higher than the prevalence 12.7% (21/165) in the general population (p < 0.001). In addition, suboptimal health prevalence was higher in female carers (50.3%; 95/189) than females in the general population (12.4%; 18/145). Logistic regression showed that the caregiving role influenced SHS, with carers 6.4 times more likely to suffer from SHS than their non-caring counterparts (aOR = 6.400, 95% CI = 3.751–10.919). Conclusions: Unpaid carers in Australia have a significantly higher prevalence of SHS than that in the general population and experience poorer health. The SHSQ-25 is a powerful tool that can be utilised to screen at-risk individuals to predict their risk of chronic disease development, an essential pillar for shifting the paradigm change from reactive medicine to that of predictive, preventive and personalised medicine (PPPM).

Background: Converging data have suggested that monocytic inflammation and C-reactive protein (CRP) are biologically intertwined processes and are involved in diabetogenesis. This study aimed to investigate the association between systemic inflammation assessed by joint cumulative high-sensitivity C-reactive protein (CumCRP) and monocyte to high-density lipoprotein ratio (CumMHR) and incident type 2 diabetes (T2D) and their predictive value for T2D in a general population. Methods: A total of 40,813 nondiabetic participants from a prospective real-life cohort (Kailuan Study, China) were followed biennially from 2010/2011 until December 31, 2020. Multivariable Cox regression analyses were conducted to evaluate the adjusted hazard ratios (aHRs) of incident diabetes. Results: During a median follow-up of 7.98 (IQR: 5.74–8.87) years, 4848 T2D cases developed. CumMHR and CumCRP were alone or jointly associated with incident T2D after adjusting for potential confounders. Elevated CumMHR levels significantly increased the risk of incident diabetes in each CumCRP strata (P-interaction: 0.0278). Participants with concomitant elevations in CumMHR and CumCRP levels had the highest risk (aHR: 1.71, 95% CI 1.52–1.91) compared to both in the low strata. Notably, the coexposure-associated T2D risk was modified by age, sex, hypertension, dyslipidemia, and prediabetes status. C-statistics increased from 0.7377 to 0.7417 when CumMHR and CumCRP were added into the multivariable-adjusted model, with a net reclassification improvement (%) of 12.39 (9.39–15.37) (P < 0.0001). Conclusions: Cumulative hsCRP and MHR were both independently and jointly associated with an increased risk of T2D and their addition to established risk factors should improve risk prediction and reclassification of diabetes.

Circular RNAs (circRNAs) play an important role in the progression of osteosarcoma. However, the precise function of circPVT1 in osteosarcoma remains elusive. This study aims to explore the molecular mechanism underlying the involvement of circPVT1 in osteosarcoma cells. We quantified circPVT1 expression using qRT-PCR in both control and osteosarcoma cell lines. To investigate the roles of circPVT1, miR-490-5p and HAVCR2 in vitro, we separately conducted overexpression and inhibition experiments for circPVT1, miR-490-5p and HAVCR2 in HOS and U2OS cells. Cell migration was assessed through wound healing and transwell migration assays, and invasion was measured via the Matrigel invasion assay. To elucidate the regulatory mechanism of circPVT1 in osteosarcoma, a comprehensive approach was employed, including fluorescence in situ hybridization, qRT-PCR, Western blot, bioinformatics, dual-luciferase reporter assay and rescue assay. CircPVT1 expression in osteosarcoma cell lines surpassed that in control cells. The depletion of circPVT1 resulted in a notable reduction in the in vitro migration and invasion of osteosarcoma cells. Mechanism experiments revealed that circPVT1 functioned as a miR-490-5p sequester, and directly targeted HAVCR2. Overexpression of miR-490-5p led to a significant attenuation of migration and invasion of osteosarcoma cells, whereas HAVCR2 overexpression had the opposite effect, promoting these abilities. Additionally, circPVT1 upregulated HAVCR2 expression via sequestering miR-490-5p, thereby orchestrating the migration and invasion in osteosarcoma cells. CircPVT1 orchestrates osteosarcoma migration and invasion by regulating the miR-490-5p/HAVCR2 axis, underscoring its potential as a promising therapeutic target for osteosarcoma.

Circular RNAs (circRNAs) play a crucial role in cancer development and progression. This study aimed to identify potential circRNA biomarkers for osteosarcoma. Articles published from January 2010 to September 2023 were searched across eight databases to compare circRNA expression profiles in osteosarcoma and control samples (human, animal and cell lines). Meta-analysis was conducted under a random effects model. Subgroup analysis of circRNAs in different samples and tissues was performed. Diagnostic value was evaluated using receiver operator characteristic curves. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis explored functions of circRNA host genes. A circRNA-miRNA-mRNA axis depicted the regulatory mechanism in osteosarcoma. Among 1356 circRNAs with differential expression were identified across 226 original studies, only 74 were reported in at least three published sub-studies. Meta-analysis identified 58 dysregulated circRNAs (52 upregulated and 6 downregulated). Eleven circRNAs consistently showed dysregulation in tissues and cell lines, with hsa_circ_0005721 showing potential as a circulating biomarker in osteosarcoma. Sensitivity analysis demonstrated 97 % consistency. The overall area under the curve was 0.87 (95 % CI, 0.83–0.89). GO and KEGG enrichment analyses revealed host gene involvement in cancer. The circRNA-miRNA-mRNA axis revealed the regulatory axis and interactions within osteosarcoma specifically. This study demonstrates circRNAs as potential diagnostic biomarkers for osteosarcoma. Consistently reported dysregulated circRNAs are potential biomarkers in osteosarcoma pathogenesis, with hsa_circ_0005721 as a potential circulating biomarker for diagnosis and treatment.

Observational epidemiological studies have reported a relationship between remnant cholesterol and stroke. However, the results are inconclusive, and causality remains unclear due to confounding or reverse causality. Our objective in this study was to investigate the causal relevance of remnant cholesterol and the risk of stroke and its subtypes using the Mendelian randomization (MR) approach. Genome-wide association studies (GWASs) including 115,082 European individuals (UK Biobank) were used to identify instruments for remnant cholesterol, including intermediate-density lipoprotein (IDL) cholesterol and very-low-density lipoprotein (VLDL) cholesterol. Summary-level data for total stroke, intracerebral hemorrhage, subarachnoid hemorrhage, ischemic stroke (IS), and IS subtypes were obtained from GWAS meta-analyses conducted by the MEGASTROKE consortium. Univariable and multivariable MR analyses were performed. The GWAS identified multiple single-nucleotide polymorphisms after clumping for remnant cholesterol (n = 52), IDL cholesterol (n = 62), and VLDL cholesterol (n = 67). Assessed individually using MR, remnant cholesterol (weighted median: odds ratio [OR] 1.32 per 1-SD higher trait; 95% CI: 1.04–1.67; P = 0.024) had effect estimates consistent with a higher risk of LAS-IS, driven by IDL cholesterol (OR 1.32; 95% CI: 1.04–1.68; P = 0.022). In multivariable MR, IDL cholesterol (OR 1.46; 95% CI: 1.10–1.93; P = 0.009) retained a robust effect on LAS-IS after controlling for VLDL cholesterol and high-density lipoprotein cholesterol. The MR analysis did not indicate causal associations between remnant cholesterol and other stroke subtypes. This study suggests that remnant cholesterol is causally associated with the risk of LAS-IS driven by IDL cholesterol.

A food composition database estimating S-methyl cysteine sulfoxide (SMCSO) was created following a systematic literature search. SMCSO data (705 entries) from 19 vegetables were summarised: brassicas (n = 10) and alliums (n = 9). The highest SMCSO in brassicas was reported in Brussels sprouts (median [range]: 318 [68−420] mg/100 g fresh weight (FW)) whilst the lowest was in radish (19 [4–45] mg/100 g FW). Brussels sprouts were almost twice as concentrated in SMCSO as cauliflower, followed by cabbage, kale, broccoli, kohlrabi, swede, Chinese cabbage, and turnips. The alliums highest in SMCSO were Chinese chives (271 [185−413] mg/100 g FW) followed by rakkyo and garlic, with substantially less found in shallots, onion, and leek. Literature reporting SMCSO content in food is sparse. Further research is required to quantify SMCSO in commercially available vegetables and other foods, in order to update and expand this database for application to large populations and future intervention studies.

Background: Obesity is a classified risk factor for several of the world’s leading causes of death. In this study, we combined information contained in body mass index (BMI), total percentage body fat (TPBF) and relative fat mass (RFM) to estimate obesity prevalence and examine the risk factors associated with obesity. Methods: The study recruited 1027 undergraduate students aged between 16 and 25 years using a cross-sectional study design and two-stage stratified random sampling between January and April 2019 from the Kwame Nkrumah University of Science and Technology, Kumasi, Ghana. Demographic, lifestyle, and family history of chronic disease data, were collected using a structured questionnaire. Bioelectrical impedance, along with height, weight, age, and gender, were used to estimate BMI and TPBF. The RFM was calculated using a published equation. The TPBF and RFM ranges were evaluated based on standard BMI thresholds and an informative combined obesity prevalence estimated in a Bayesian framework. Multiple logistic regression analysis was used to evaluate potential risk factors of overweight/obesity. Results: Concordance between BMI, TPBF and RFM for obesity classification was 84% among female and 82.9% among male students. The Bayesian analysis revealed a combined prevalence means of obesity of 9.4% (95%CI: 6.9-12.2%) among female students and 6.7% (95%CI:4.3-9.5%) among male students. The odds of obesity were increased between 1.8 and 2.5 for females depending on the classification index. A significant increasing trend of obesity was observed with university-level. A family history of obesity was associated with a high estimate of general, central, and high TPBF. Conclusion: Using multiple adiposity indicators conjointly in a Bayesian framework offers a greater power to examine obesity prevalence. We have applied this and reported high obesity prevalence, especially among female students. University level and family history of obesity were key determinants f

Background: Adiposity and elevated inflammation are two hallmarks of hyperglycemia. However, it is unknown whether clustering of elevated inflammation and adiposity interact act on diabetogenesis and lead to a greater risk for incident type 2 diabetes (T2D). Methods: Adiposity was indicated by body mass index, waist circumference and ultrasonography-measured fatty liver degrees. Elevated inflammation was indicated as high-sensitivity C-reactive protein levels ≥ 2 mg/L. Time-to-event survival analyses were conducted to investigate the joint effect of adiposity and inflammation on incident T2D on both multiplicative and additive scales. Results: Among 82,172 non-diabetic participants from a prospective cohort in China, 14,278 T2D occurred over a median follow-up of 11 years. In the multivariable-adjusted model, elevated inflammation [1.12 (1.08‒1.16)] and adiposity [1.76 (1.69‒1.83) for overweight/obesity, 1.49 (1.44‒1.55) for central obesity, and 2.02 (1.95‒2.09) for fatty liver] were significantly associated with incident diabetes. Higher adiposity-associated risks and incidence rates of diabetes were observed with elevated inflammation. When studying the joint effect, the adjusted HRs were 1.77 (1.69‒1.85) for overweight/obesity, 1.14 (1.06‒1.23) for elevated inflammation, and 2.08 (1.97‒2.19) for their joint effect, with a relative excess risk due to interaction of 0.17 (0.05‒0.28). The attributable proportions were 71.30% for overweight/obesity, 12.96% for elevated inflammation, and 15.74% for their interaction. Similar results were observed when adiposity was assessed as waist circumference or fatty liver. Conclusions: Adiposity and elevated inflammation synergically lead to greater risks of incident diabetes than addition of each individual exposure. Strategies simultaneously targeting both risks should produce more benefits for diabetes prevention than through initiatives directed at each separate risk.

The use of an altered immunoglobulin G (IgG) N-glycan pattern as an inflammation metric has been reported in subclinical atherosclerosis and metabolic disorders, both of which are important risk factors in cardiovascular health. However, the usable capacity of IgG N-glycosylation profiles for the risk stratification of cardiovascular diseases (CVDs) remains unknown. This study aimed to develop a cardiovascular aging index for tracking cardiovascular risk using IgG N-glycans. This cross-sectional investigation enrolled 1465 individuals aged 40–70 years from the Busselton Healthy and Ageing Study. We stepwise selected the intersection of altered N-glycans using feature-selection methods in machine learning (recursive feature elimination and penalized regression algorithms) and developed an IgG N-glycosylation cardiovascular age (GlyCage) index to reflect the deviation from calendar age attributable to cardiovascular risk. The strongest contributors to GlyCage index were fucosylated N-glycans with bisecting N-acetylglucosamine (GlcNAc) (glycan peak 6 (GP6), FA2B,) and digalactosylated N-glycans with bisecting GlcNAc (GP13, A2BG2). A one-unit increase of GlyCage was significantly associated with a higher Framingham ten-year cardiovascular risk (odds ratio (OR), 1.09; 95% confidence interval (95% CI): 1.05–1.13) and probability of CVDs (OR, 1.07; 95% CI: 1.01–1.13) independent of calendar age. Individuals with excessive GlyCage (exceeding a calendar age > 3 years) had an increased cardiovascular risk and probability of CVDs, with adjusted ORs of 2.22 (95% CI: 1.41–3.53) and 2.71 (95% CI: 1.25–6.41), respectively. The area under curve (AUC) values of discriminating high cardiovascular risk and events were 0.73 and 0.65 for GlyCage index, and 0.65 and 0.63 for calendar age. The GlyCage index developed in this study can thus be used to track cardiovascular health using IgG N-glycosylation profiles. The distance between GlyCage and calendar age independently indicates the ca

Background: Both elevated inflammation and atherogenic dyslipidemia are prominent in young-onset diabetes and are increasingly identified as biologically intertwined processes that contribute to diabetogenesis. We aimed to investigate the age-specific risks of type 2 diabetes (T2D) upon concomitant chronic inflammation and atherogenic dyslipidemia. Methods: Age-stratified Cox regression analysis of the risk of incident diabetes upon co-exposure to time-averaged cumulative high-sensitivity C-reactive protein (CumCRP) and atherogenic index of plasma (CumAIP) among 42,925 nondiabetic participants from a real-world, prospective cohort (Kailuan Study). Results: During a median 6.41 years of follow-up, 3987 T2D developed. Isolated CumAIP and CumCRP were significantly associated with incident T2D in the entire cohort and across all age subgroups. Both CumAIP and CumCRP were jointly associated with an increased risk of diabetes (P-interaction = 0.0126). Compared to CumAIP < -0.0699 and CumCRP < 1 mg/L, co-exposure to CumAIP ≥ − 0.0699 and CumCRP ≥ 3 mg/L had a significant hazard ratio (HR) [2.55 (2.23–2.92)] after adjusting for socio-demographic, life-style factors, family history of diabetes, blood pressure, renal function and medication use. The co-exposure-associated risks varied greatly by age distribution (P-interaction = 0.0193): < 40 years, 6.26 (3.47–11.28); 40–49 years, 2.26 (1.77–2.89); 50–59 years, 2.51 (2.00–3.16); 60–69 years, 2.48 (1.86–3.30); ≥ 70 years, 2.10 (1.29–3.40). In young adults ( < 45 years), both exposures had a significant supra-additive effect on diabetogenesis (relative excess risk due to interaction: 0.80, 95% CI 0.10–1.50). Conclusions: These findings highlight the need for age-specific combined assessment and management of chronic inflammation and dyslipidemia in primary prevention against T2D, particularly for young adults. The clinical benefit derived from dual-target intervention against dyslipidemia and inflammation will exceed the sum of

The coronavirus disease 2019 (COVID-19) pandemic has continued for more than 3 years, placing a huge burden on society worldwide. Although the World Health Organization (WHO) has declared an end to COVID-19 as a Public Health Emergency of International Concern (PHEIC), it is still considered a global threat. Previously, there has been a long debate as to whether the COVID-19 emergency will eventually end or transform into a more common infectious disease from a PHEIC, and how should countries respond to similar pandemics in the future more time-efficiently and cost-effectively. We reviewed the past, middle and current situation of COVID-19 based on bibliometric analysis and epidemiological data. Thereby, the necessity is indicated to change the paradigm from reactive healthcare services to predictive, preventive and personalised medicine (PPPM) approach, in order to effectively protect populations against COVID-19 and any future pandemics. Corresponding measures are detailed in the article including the involvement of multi-professional expertise, application of artificial intelligence, rapid diagnostics and patient stratification, and effective protection, amongst other to be considered by advanced health policy.

Sulfur is essential for the health of plants and is an indispensable dietary component for human health and disease prevention. Its incorporation into our food supply is heavily reliant upon the uptake of sulfur into plant tissue and our subsequent intake. Dietary requirements for sulfur are largely calculated based upon requirements for the sulfur-containing amino acids (SAA), cysteine and methionine, to meet the demands for synthesis of proteins, enzymes, co-enzymes, vitamins, and hormones. SAA are found in abundance in animal sources and are relatively low in plants. However, some plants, particularly cruciferous and allium vegetables, produce many protective sulfur-containing secondary metabolites, such as glucosinolates and cysteine sulfoxides. The variety and quantity of these sulfur-containing metabolites are extensive and their effects on human health are wide-reaching. Many benefits appear to be related to sulfur’s role in redox biochemistry, protecting against uncontrolled oxidative stress and inflammation; features consistent within cardiometabolic dysfunction and many chronic metabolic diseases of aging. This narrative explores the origins and importance of sulfur, its incorporation into our food supply and dietary sources. It also explores the overarching potential of sulfur for human health, particularly around the amelioration of oxidative stress and chronic inflammation, and subsequent chronic disease prevention.

Endothelial glycocalyx (EG) shedding is associated with septic shock and described following intravenous (IV) fluid administration. To investigate the possible impact of IV fluids on the pathobiology of septic shock we investigated associations between biomarkers of EG shedding and endothelial cell activation, and relationships with IV fluid volume. Serum samples were obtained on admission (T0) and at 24 h (T24) in patients undergoing haemodynamic resuscitation for suspected septic shock in the emergency department. Biomarkers of EG shedding—Syndecan-1 (Syn-1), Syndecan-4 (Syn-4), Hyaluronan, endothelial activation—Endothelin-1 (ET-1), Angiopoeitin-2 (Ang-2), Vascular Endothelial Growth Factor Receptor-1(VEGF-1) and leucocyte activation/inflammation—Resistin, Neutrophil Gelatinase Associated Lipocalin (NGAL) and a marker of cardiac stretch—Pro-Atrial Natriuretic Peptide (Pro-ANP) were compared to the total IV fluid volume administered using Tobit regression. Data on 86 patients (52 male) with a mean age of 60 (SD 18) years were included. The mean fluid volume administered to T24 was 4038 ml (SD 2507 ml). No significant association between fluid volume and Pro-ANP or any of the biomarkers were observed. Syn-1 and Syn-4 were significantly correlated with each other (Spearman Rho 0.43, p < 0.001) but not with Hyaluronan. Syn-1 and Syn-4 both correlated with VEGFR-1 (Rho 0.56 and 0.57 respectively, p < 0.001) whereas Hyaluronan correlated with ET-1 (Rho 0.43, p < 0.001) and Ang-2 (Rho 0.43, p < 0.001). There was no correlation between Pro-ANP and any of the EG biomarkers. Distinct patterns of association between biomarkers of EG shedding and endothelial cell activation were observed among patients undergoing resuscitation for sepsis. No relationship between IV fluid volume and Pro-ANP or any of the other biomarkers was observed.

Background: Recent studies have established that monocyte-derived inflammation plays a central role in the pathogenesis of type 2 diabetes mellitus (T2DM). It is unclear whether chronic metabolic inflammation, reflected by the cumulative monocyte to high-density lipoprotein ratio (CumMHR), predisposes the general population to T2DM. Methods: This study included 40,813 participants without diabetes from a real-life, community-based cohort (the Kailuan Study) attending a 2-year cycle of health survey since 2006. Cumulative exposure was obtained from 2006/2007 to 2010/2011. Follow-up started at 2010/2011 and through 2020. Multivariable-adjusted Cox regression models were used to calculate the CumMHR-associated risk of incident T2DM. Results: Over a median follow-up period of 7.98 (IQR: 5.74 – 8.87) years, 4,848 T2DM cases occurred. The CumMHR was positively associated with the risk of incident T2DM after adjusting for age, sex, smoking, drinking habits, physical activities, BMI, triglyceride-glycemia index, log(leukocyte count), log(hsCRP), blood pressure, renal function, and medication uses with adjusted HRs of 1.0 (ref.), 1.18 (1.05 ‒ 1.25), 1.17 (1.07 ‒ 1.27), 1.38 (1.26 ‒ 1.50), respectively, in CumMHR Quartiles 1, 2, 3 and 4. When follow-up ended at 2014/2015, the short-term (4 ‒ year) adjusted T2DM risks in CumMHR Quartiles 2, 3, and 4 were 1.14 (1.01 ‒ 1.29), 1.17 (1.04 ‒ 1.32), 1.40 (1.25 ‒ 1.58), respectively, relative to Quartile 1. A significant interaction between CumMHR and cumulative high-sensitivity C-reactive protein (CumCRP) was observed (P-interaction: 0.0109). The diabetic risk in the highest quartile of CumMHR was higher (1.53 [1.28 ‒ 1.84]) when CumCRP < 1 mg/L, attenuated with increasing CumCRP levels (1 ~ 10 mg/L) and disappeared in CumCRP ≥ 10 mg/L. Hypertension, overweight, or smoking habits further modified the CumMHR-associated diabetic risk. Conclusions: Cumulative MHR may be a promising supplement to hsCRP for more comprehensively assessing

Spondyloarthritis (SpA) is a group of chronic inflammatory arthritic diseases causing inflammatory back pain and stiffness, leading to irreversible damage of joint and spine, seriously affecting the quality of life. However, the exact pathogenesis of SpA is still unknown, although the blockers of tumor necrosis factor (TNF) are a major therapeutic advance. Of interest is the association between SpA and Immunoglobulin G (IgG) N-glycosylation. IgG N-glycosylation is a process of post-translational modification (PTM) that takes part in regulating anti- and pro-inflammatory effects. A relationship between IgG N-glycosylation and the development of inflammatory arthritic diseases exists, in addition this relationship often occurs before the onset of disease. There are studies reporting the association between IgG N-glycosylation and SpA, leading to a significant amount of data being generated. Analysis of this data in a rigorous form is greatly needed, hence this review will focus on identifying the relationships that exist between IgG N-glycosylation in inflammatory arthritis. More specifically, the modification to the structure of IgG N-glycosylation via TNF blockers as a treatment, the link between disease activity and IgG N-glycosylation, and the predictive capacity of IgG N-glycosylation in SpA. Investigation of IgG N-glycosylation has demonstrated that IgG N-galactosylation plays an important role in the development and prognosis of SpA. This association provides a novel pathway to further research to improve early diagnosis and possible biomarkers for treatment of patients with SpA.

Endothelial glycocalyx (EG) shedding is associated with septic shock and described following intravenous (IV) fluid administration. To investigate the possible impact of IV fluids on the pathobiology of septic shock we investigated associations between biomarkers of EG shedding and endothelial cell activation, and relationships with IV fluid volume. Serum samples were obtained on admission (T0) and at 24 h (T24) in patients undergoing haemodynamic resuscitation for suspected septic shock in the emergency department. Biomarkers of EG shedding—Syndecan-1 (Syn-1), Syndecan-4 (Syn-4), Hyaluronan, endothelial activation—Endothelin-1 (ET-1), Angiopoeitin-2 (Ang-2), Vascular Endothelial Growth Factor Receptor-1(VEGF-1) and leucocyte activation/inflammation—Resistin, Neutrophil Gelatinase Associated Lipocalin (NGAL) and a marker of cardiac stretch—Pro-Atrial Natriuretic Peptide (Pro-ANP) were compared to the total IV fluid volume administered using Tobit regression. Data on 86 patients (52 male) with a mean age of 60 (SD 18) years were included. The mean fluid volume administered to T24 was 4038 ml (SD 2507 ml). No significant association between fluid volume and Pro-ANP or any of the biomarkers were observed. Syn-1 and Syn-4 were significantly correlated with each other (Spearman Rho 0.43, p < 0.001) but not with Hyaluronan. Syn-1 and Syn-4 both correlated with VEGFR-1 (Rho 0.56 and 0.57 respectively, p < 0.001) whereas Hyaluronan correlated with ET-1 (Rho 0.43, p < 0.001) and Ang-2 (Rho 0.43, p < 0.001). There was no correlation between Pro-ANP and any of the EG biomarkers. Distinct patterns of association between biomarkers of EG shedding and endothelial cell activation were observed among patients undergoing resuscitation for sepsis. No relationship between IV fluid volume and Pro-ANP or any of the other biomarkers was observed.

Sulfur is essential for the health of plants and is an indispensable dietary component for human health and disease prevention. Its incorporation into our food supply is heavily reliant upon the uptake of sulfur into plant tissue and our subsequent intake. Dietary requirements for sulfur are largely calculated based upon requirements for the sulfur-containing amino acids (SAA), cysteine and methionine, to meet the demands for synthesis of proteins, enzymes, co-enzymes, vitamins, and hormones. SAA are found in abundance in animal sources and are relatively low in plants. However, some plants, particularly cruciferous and allium vegetables, produce many protective sulfur-containing secondary metabolites, such as glucosinolates and cysteine sulfoxides. The variety and quantity of these sulfur-containing metabolites are extensive and their effects on human health are wide-reaching. Many benefits appear to be related to sulfur’s role in redox biochemistry, protecting against uncontrolled oxidative stress and inflammation; features consistent within cardiometabolic dysfunction and many chronic metabolic diseases of aging. This narrative explores the origins and importance of sulfur, its incorporation into our food supply and dietary sources. It also explores the overarching potential of sulfur for human health, particularly around the amelioration of oxidative stress and chronic inflammation, and subsequent chronic disease prevention.

Type 2 diabetes mellitus (T2DM) has been strongly associated with single nucleotide polymorphisms (SNPs) in the TCF7L2 gene. This study investigated the association between rs12255372, rs7903146 in the TCF7L2 gene and T2DM in a Ghanaian population. A case-control study design was used for this study. A total of 106 T2DM patients and 110 control participants were selected. Basic data collected included body mass index, blood pressure and socio-demographics. Fasting blood samples were collected and processed for: serum lipid analysis, plasma glucose estimation and plasma HbA1c estimation. Parts of the whole blood samples were used for DNA extraction using a modified salting-out method. Common and allele-specific primers were designed for genotyping using the Modified Tetra-Primer Amplification assay. Associations were evaluated using logistic regression models. The rs7903146 risk variant was significantly associated with 2.16 vs. 4.06 increased odds for T2DM in patients <60 years vs. ≥60 years. Both rs7903146 and rs12255372 were significantly associated with increased odds of T2DM in women, overweight/obese, T2DM negative family history (T2DM-NFH) and low-HDL-C. In a multivariate model, rs7903146 but not rs12255372 was significantly associated with 2.18, 5.01 and 2.25 increased odds of T2DM, under the codominant, recessive and additive model, respectively (p < 0.05). The association between rs7903146 and rs12255372 with T2DM is more highly associated in a subgroup—women and those with T2DM-NFH, yet who have cardiometabolic risk.

Type 2 diabetes mellitus (T2DM) has been strongly associated with single nucleotide polymorphisms (SNPs) in the TCF7L2 gene. This study investigated the association between rs12255372, rs7903146 in the TCF7L2 gene and T2DM in a Ghanaian population. A case-control study design was used for this study. A total of 106 T2DM patients and 110 control participants were selected. Basic data collected included body mass index, blood pressure and socio-demographics. Fasting blood samples were collected and processed for: serum lipid analysis, plasma glucose estimation and plasma HbA1c estimation. Parts of the whole blood samples were used for DNA extraction using a modified salting-out method. Common and allele-specific primers were designed for genotyping using the Modified Tetra-Primer Amplification assay. Associations were evaluated using logistic regression models. The rs7903146 risk variant was significantly associated with 2.16 vs. 4.06 increased odds for T2DM in patients <60 years vs. ≥60 years. Both rs7903146 and rs12255372 were significantly associated with increased odds of T2DM in women, overweight/obese, T2DM negative family history (T2DM-NFH) and low-HDL-C. In a multivariate model, rs7903146 but not rs12255372 was significantly associated with 2.18, 5.01 and 2.25 increased odds of T2DM, under the codominant, recessive and additive model, respectively (p < 0.05). The association between rs7903146 and rs12255372 with T2DM is more highly associated in a subgroup—women and those with T2DM-NFH, yet who have cardiometabolic risk.

© 2020 by the authors. Licensee MDPI, Basel, Switzerland. Genetic variants that are associated with susceptibility to type 2 diabetes (T2D) are important for identification of individuals at risk and can provide insights into the molecular basis of disease. Analysis of T2D in domestic animals provides both the opportunity to improve veterinary management and breeding programs as well as to identify novel T2D risk genes. Australian-bred Burmese (ABB) cats have a 4-fold increased incidence of type 2 diabetes (T2D) compared to Burmese cats bred in the United States. This is likely attributable to a genetic founder effect. We investigated this by performing a genome-wide association scan on ABB cats. Four SNPs were associated with the ABB T2D phenotype with p values < 0.005. All exons and splice junctions of candidate genes near significant single-nucleotide polymorphisms (SNPs) were sequenced, including the genes DGKG, IFG2BP2, SLC8A1, E2F6, ETV5, TRA2B and LIPH. Six candidate polymorphisms were followed up in a larger cohort of ABB cats with or without T2D and also in Burmese cats bred in America, which exhibit low T2D incidence. The original SNPs were confirmed in this cohort as associated with the T2D phenotype, although no novel coding SNPs in any of the seven candidate genes showed association with T2D. The identification of genetic markers associated with T2D susceptibility in ABB cats will enable preventative health strategies and guide breeding programs to reduce the prevalence of T2D in these cats.

© 2020 by the authors. Licensee MDPI, Basel, Switzerland. Genetic variants that are associated with susceptibility to type 2 diabetes (T2D) are important for identification of individuals at risk and can provide insights into the molecular basis of disease. Analysis of T2D in domestic animals provides both the opportunity to improve veterinary management and breeding programs as well as to identify novel T2D risk genes. Australian-bred Burmese (ABB) cats have a 4-fold increased incidence of type 2 diabetes (T2D) compared to Burmese cats bred in the United States. This is likely attributable to a genetic founder effect. We investigated this by performing a genome-wide association scan on ABB cats. Four SNPs were associated with the ABB T2D phenotype with p values < 0.005. All exons and splice junctions of candidate genes near significant single-nucleotide polymorphisms (SNPs) were sequenced, including the genes DGKG, IFG2BP2, SLC8A1, E2F6, ETV5, TRA2B and LIPH. Six candidate polymorphisms were followed up in a larger cohort of ABB cats with or without T2D and also in Burmese cats bred in America, which exhibit low T2D incidence. The original SNPs were confirmed in this cohort as associated with the T2D phenotype, although no novel coding SNPs in any of the seven candidate genes showed association with T2D. The identification of genetic markers associated with T2D susceptibility in ABB cats will enable preventative health strategies and guide breeding programs to reduce the prevalence of T2D in these cats.

Genetic variation conferring resistance and susceptibility to carcinogen-induced tumorigenesis is frequently studied in mice. We have now turned this idea to melanoma using the collaborative cross (CC), a resource of mouse strains designed to discover genes for complex diseases. We studied melanoma-prone transgenic progeny across seventy CC genetic backgrounds. We mapped a strong quantitative trait locus for rapid onset spontaneous melanoma onset to Prkdc, a gene involved in detection and repair of DNA damage. In contrast, rapid onset UVR-induced melanoma was linked to the ribosomal subunit gene Rrp15. Ribosome biogenesis was upregulated in skin shortly after UVR exposure. Mechanistically, variation in the ‘usual suspects’ by which UVR may exacerbate melanoma, defective DNA repair, melanocyte proliferation, or inflammatory cell infiltration, did not explain melanoma susceptibility or resistance across the CC. Instead, events occurring soon after exposure, such as dysregulation of ribosome function, which alters many aspects of cellular metabolism, may be important.

Genetic factors influence susceptibility to diabetic kidney disease. Here we mapped genes mediating renal hypertrophic changes in response to diabetes. A survey of 15 mouse strains identified variation in diabetic kidney hypertrophy. Strains with greater (FVB/N(FVB)) and lesser (C57BL/6 (B6)) responses were crossed and diabetic F2 progeny were characterized. Kidney weights of diabetic F2 mice were broadly distributed. Quantitative trait locus analyses revealed diabetic mice with kidney weights in the upper quartile shared alleles on chromosomes (chr) 6 and 12; these loci were designated as Diabetic kidney hypertrophy (Dkh)-1 and -2. To confirm these loci, reciprocal congenic mice were generated with defined FVB chromosome segments on the B6 strain background (B6.Dkh1/2f) or vice versa (FVB.Dkh1/2b). Diabetic mice of the B6.Dkh1/2f congenic strain developed diabetic kidney hypertrophy, while the reciprocal FVB.Dkh1/2b congenic strain was protected. The chr6 locus contained the candidate gene; Ark1b3, coding aldose reductase; the FVB allele has a missense mutation in this gene. Microarray analysis identified differentially expressed genes between diabetic B6 and FVB mice. Thus, since the two loci identified by quantitative trait locus mapping are syntenic with regions identified for human diabetic kidney disease, the congenic strains we describe provide a valuable new resource to study diabetic kidney disease and test agents that may prevent it.

Clinical variation in patient responses to myocardial infarction (MI) has been difficult to model in laboratory animals. To assess the genetic basis of variation in outcomes after heart attack, we characterized responses to acute MI in the Collaborative Cross (CC), a multi-parental panel of genetically diverse mouse strains. Striking differences in post-MI functional, morphological, and myocardial scar features were detected across 32 CC founder and recombinant inbred strains. Transcriptomic analyses revealed a plausible link between increased intrinsic cardiac oxidative phosphorylation levels and MI-induced heart failure. The emergence of significant quantitative trait loci for several post-MI traits indicates that utilizing CC strains is a valid approach for gene network discovery in cardiovascular disease, enabling more accurate clinical risk assessment and prediction.

Genetic factors influence susceptibility to diabetic kidney disease. Here we mapped genes mediating renal hypertrophic changes in response to diabetes. A survey of 15 mouse strains identified variation in diabetic kidney hypertrophy. Strains with greater (FVB/N(FVB)) and lesser (C57BL/6 (B6)) responses were crossed and diabetic F2 progeny were characterized. Kidney weights of diabetic F2 mice were broadly distributed. Quantitative trait locus analyses revealed diabetic mice with kidney weights in the upper quartile shared alleles on chromosomes (chr) 6 and 12; these loci were designated as Diabetic kidney hypertrophy (Dkh)-1 and -2. To confirm these loci, reciprocal congenic mice were generated with defined FVB chromosome segments on the B6 strain background (B6.Dkh1/2f) or vice versa (FVB.Dkh1/2b). Diabetic mice of the B6.Dkh1/2f congenic strain developed diabetic kidney hypertrophy, while the reciprocal FVB.Dkh1/2b congenic strain was protected. The chr6 locus contained the candidate gene; Ark1b3, coding aldose reductase; the FVB allele has a missense mutation in this gene. Microarray analysis identified differentially expressed genes between diabetic B6 and FVB mice. Thus, since the two loci identified by quantitative trait locus mapping are syntenic with regions identified for human diabetic kidney disease, the congenic strains we describe provide a valuable new resource to study diabetic kidney disease and test agents that may prevent it.

Clinical variation in patient responses to myocardial infarction (MI) has been difficult to model in laboratory animals. To assess the genetic basis of variation in outcomes after heart attack, we characterized responses to acute MI in the Collaborative Cross (CC), a multi-parental panel of genetically diverse mouse strains. Striking differences in post-MI functional, morphological, and myocardial scar features were detected across 32 CC founder and recombinant inbred strains. Transcriptomic analyses revealed a plausible link between increased intrinsic cardiac oxidative phosphorylation levels and MI-induced heart failure. The emergence of significant quantitative trait loci for several post-MI traits indicates that utilizing CC strains is a valid approach for gene network discovery in cardiovascular disease, enabling more accurate clinical risk assessment and prediction.

Genetic variation conferring resistance and susceptibility to carcinogen-induced tumorigenesis is frequently studied in mice. We have now turned this idea to melanoma using the collaborative cross (CC), a resource of mouse strains designed to discover genes for complex diseases. We studied melanoma-prone transgenic progeny across seventy CC genetic backgrounds. We mapped a strong quantitative trait locus for rapid onset spontaneous melanoma onset to Prkdc, a gene involved in detection and repair of DNA damage. In contrast, rapid onset UVR-induced melanoma was linked to the ribosomal subunit gene Rrp15. Ribosome biogenesis was upregulated in skin shortly after UVR exposure. Mechanistically, variation in the ‘usual suspects’ by which UVR may exacerbate melanoma, defective DNA repair, melanocyte proliferation, or inflammatory cell infiltration, did not explain melanoma susceptibility or resistance across the CC. Instead, events occurring soon after exposure, such as dysregulation of ribosome function, which alters many aspects of cellular metabolism, may be important.

Purpose: Examination of the vessels of the retina provides an insight into the health of the eye. Variation in the number of major retinal blood vessels may indicate development of various diseases. Identification of mouse strains with a varied number of vessels will be useful to understand the genetic basis for, and the physiological consequences of, such variation. We therefore analyzed variation in retinal vasculature among strains of the next-generation genetic resource, The Collaborative Cross (CC). Methods: The retinal vasculature from both flat mounted whole-retina and histology sections were examined in our panel of CC and common inbred mouse strains, to characterize the vascular pattern. In the course of this work, we optimized the trypsin digest method for examination of fragile retinal samples. We describe our optimized method, providing a step-by-step protocol and list of specific tools to isolate the vascular network. Results: The CC strains showed wide variation in numbers of the major retinal arteries and veins. One strain had only a single capillary network. Our modified method was able to isolate the retinal vasculature successfully and was particularly suited to strains with minimal neural structure. Conclusions: Different retinal anatomy, with wide variation in the numbers of retinal arteries and veins was observed and could be explained by genetic variation. Our optimized trypsin digest method can be applied to study ocular vasculature pathology in any retinal disease in humans or animal models

Purpose: Examination of the vessels of the retina provides an insight into the health of the eye. Variation in the number of major retinal blood vessels may indicate development of various diseases. Identification of mouse strains with a varied number of vessels will be useful to understand the genetic basis for, and the physiological consequences of, such variation. We therefore analyzed variation in retinal vasculature among strains of the next-generation genetic resource, The Collaborative Cross (CC). Methods: The retinal vasculature from both flat mounted whole-retina and histology sections were examined in our panel of CC and common inbred mouse strains, to characterize the vascular pattern. In the course of this work, we optimized the trypsin digest method for examination of fragile retinal samples. We describe our optimized method, providing a step-by-step protocol and list of specific tools to isolate the vascular network. Results: The CC strains showed wide variation in numbers of the major retinal arteries and veins. One strain had only a single capillary network. Our modified method was able to isolate the retinal vasculature successfully and was particularly suited to strains with minimal neural structure. Conclusions: Different retinal anatomy, with wide variation in the numbers of retinal arteries and veins was observed and could be explained by genetic variation. Our optimized trypsin digest method can be applied to study ocular vasculature pathology in any retinal disease in humans or animal models

The Collaborative Cross (CC) was designed to facilitate rapid gene mapping and consists of hundreds of recombinant inbred lines descended from eight diverse inbred founder strains. A decade in production, it can now be applied to mapping projects. Here, we provide a proof of principle for rapid identification of major-effect genes using the CC. To do so, we chose coat color traits since the location and identity of many relevant genes are known. We ascertained in 110 CC lines six different coat phenotypes: albino, agouti, black, cinnamon, and chocolate coat colors and the white-belly trait. We developed a pipeline employing modifications of existing mapping tools suitable for analyzing the complex genetic architecture of the CC. Together with analysis of the founders’ genome sequences, mapping was successfully achieved with sufficient resolution to identify the causative genes for five traits. Anticipating the application of the CC to complex traits, we also developed strategies to detect interacting genes, testing joint effects of three loci. Our results illustrate the power of the CC and provide confidence that this resource can be applied to complex traits for detection of both qualitative and quantitative trait loci.

The Collaborative Cross (CC) was designed to facilitate rapid gene mapping and consists of hundreds of recombinant inbred lines descended from eight diverse inbred founder strains. A decade in production, it can now be applied to mapping projects. Here, we provide a proof of principle for rapid identification of major-effect genes using the CC. To do so, we chose coat color traits since the location and identity of many relevant genes are known. We ascertained in 110 CC lines six different coat phenotypes: albino, agouti, black, cinnamon, and chocolate coat colors and the white-belly trait. We developed a pipeline employing modifications of existing mapping tools suitable for analyzing the complex genetic architecture of the CC. Together with analysis of the founders’ genome sequences, mapping was successfully achieved with sufficient resolution to identify the causative genes for five traits. Anticipating the application of the CC to complex traits, we also developed strategies to detect interacting genes, testing joint effects of three loci. Our results illustrate the power of the CC and provide confidence that this resource can be applied to complex traits for detection of both qualitative and quantitative trait loci.

Sequence analysis of a 237 kb genomic fragment from the central region of the MHC has revealed that the HLA-B and HLA-C genes are contained within duplicated segments peri-B (53 kb) and peri-C (48 kb), respectively, and separated by an intervening sequence (IF) of 30 kb. The peri-B and peri-C segments share at least 90% sequence homology except when interrupted by insertions/deletions including Alu, L1, an endogenous retrovirus, and pseudogenes. The sequences of peri-B, IF, and peri-C were searched for the presence of Alu elements to use as markers of evolution, chromosomal rearrangements, and polymorphism. Of 29 Alu elements, 14 were identified in peri-B, 11 in peri-C, and 4 in IF. The Alu elements in peri-B and peri-C clustered phylogenetically into two clades which were classified as ``preduplication'' and ``postduplication'' clades. Four Alu J elements that are shared by peri-B and peri-C and are flanked by homologous sequences in their paralogous locations, respectively, clustered into a ``preduplication'' clade. By contrast, the majority of Alu elements, which are unique to either peri-B or peri-C, clustered into a postduplication clade together with the Alu consensus subfamily members ranging from platyrrhine-specific (Spqxcg) to catarrhine-specific Alu sequences (Y). The insertion of platyrrhine-specific Alu elements in postduplication locations of peri-B and peri-C implies that these two segments are the products of a duplication which occurred in primates prior to the divergence of the New World primate from the human lineage (35–44 mya). Examination of the paralogous Alu integration sites revealed that 9 of 14 postduplication Alu sequences have produced microsatellites of different length and sequence within the Alu 3′-poly A tail. The present analysis supports the hypothesis that HLA-B and HLA-C genes are products of an extended segmental duplication between 44 and 81 million years ago (mya), and that subsequent diversification of both genomic segments o

Wang, X., Zhong, Z., Balmer, L., & Wang, W. (2021). Glycosylation profiling as a biomarker of suboptimal health status for chronic disease stratification. In G. Lauc & I. Trbojević-Akmačić (Eds.), The role of glycosylation in health and disease (pp. 321-339). Springer, Cham. https://doi.org/10.1007/978-3-030-70115-4_16

Ram, R., Mehta, M., Balmer, L. A., Gatti, D., & Morahan, G. (2014). Rapid identification of major-effect genes using the collaborative cross. Genetics: a periodical record of investigations bearing on heredity and variation, 198(1), 75-86. Available here

Salimova, E., Nowak, K. J., Estrada, A. C., Furtado, M. B., McNamara, E., Nguyen, Q., ... Rosenthal, N. A. (2019). Variable outcomes of human heart attack recapitulated in genetically diverse mice. Nature Partner Journals Regenerative Medicine, 4(1), Article 5. Available here

Balmer, L., O’Leary, C. A., Menotti-Raymond, M., David, V., O’Brien, S., Penglis, B., … Morahan, G. (2020). Mapping of diabetes susceptibility loci in a domestic cat breed with an unusually high incidence of diabetes mellitus. Genes, 11(11), article 1369. https://doi.org/10.3390/genes11111369

Jo, Y., Balmer, L., Lee, B., Shim, J. A., Ali, L. A., Morahan, G., & Hong, C. (2020). Variants of innate CD8+ T cells are associated with Grip2 and Klf15 genes. Cellular & Molecular Immunology, 1-3. https://doi.org/10.1038/s41423-019-0357-3

This is an Author's Accepted Manuscript of: Balmer, L. A., Whiting, R., Rudnicka, C., Gallo, L. A., Jandeleit, K. A., Chow, Y., ... Morahan, G. (2019). Genetic characterization of early renal changes in a novel mouse model of diabetic kidney disease. Kidney International, 96(4), 918-926. Available http://creativecommons.org/licenses/by-nc-nd/4.0/

Ferguson, B., Handoko, H. Y., Mukhopadhyay, P., Chitsazan, A., Balmer, L., Morahan, G., & Walker, G. J. (2019). Different genetic mechanisms mediate spontaneous versus UVR-induced malignant melanoma. eLife, 8, Article e42424. Available here

Morahan, G. (2017). Genetic Variation in the Retinal Vasculature of the Collaborative Cross. Ophthalmology and Vision Sci-ence, 1, 36-45. Available here

Collin, R., Balmer, L., Morahan, G., & Lesage, S. (2019). Common heritable immunological variations revealed in genetically diverse inbred mouse strains of the collaborative cross. Journal of Immunology, 202(3), 777-786. Available here

Andrikopoulos, S., Fam, B. C., Holdsworth, A., Visinoni, S., Ruan, Z., Stathopoulos, M., ... & Proietto, J. (2016). Identification of ABCC8 as a contributory gene to impaired early-phase insulin secretion in NZO mice. Journal of Endocrinology, 228(1), 61-73. Available here